Studies were performed to examine the human immune response in normal individuals and in patients with congenital and acquired immunodeficiency states associated with a high frequency of cancer. Interleukin-2 (IL-2) and the IL-2 receptor (IL-2R) expressed on hematopoietic cells play pivotal roles in the immune response. We previously discovered a soluble form of the IL-2R (sIL-2R) and demonstrated abnormal levels of this sIL-2R in the serum of patients with a variety of diseases. A recently discovered lymphokine, interleukin-15 (IL-5), shares many functional properties with IL-2. We have shown that IL-15 stimulates the release of sIL-2R from both resting and activated cells in vitro which raises the possibility that IL-15 may contribute to the activation of the immune response and pathogenesis of disease states in which sIL-2R levels are elevated. Investigations continued on the primary immunodeficiency disorders. Examination of the tyrosine kinase (BTK) responsible for X-linked agammaglobulinemia (XLA) in patients with X-linked agammaglobulinemia and isolated growth hormone deficiency (XLA/GHD) revealed a normal abundance/normal length BTK transcript, a normal BTK sequence, and normal levels of BTK protein. These studies establish that XLA/GHD is distinct from XLA and suggest additional X-chromosome genes responsible for B-cell development. The function of the protein product of the gene responsible for the Wiskott-Aldrich Syndrome (WASP) has not been defined. We have produced a panel of monoclonal antibodies to WASP and are studying its function in normal and abnormal leukocyte function. The protein is expressed in platelets, monocytes, T-cells and B-cells. Some patients with the Wiskott- Aldrich syndrome produce the protein while others do not - suggesting heterogeneity among patients. B-cell lines from patients who fail to produce the protein will serve as the target for gene therapy experiments.